TGF-beta has been implicated in T regulatory cell (Treg) activity, and since Treg cells frequently express the CD4+CD25+ phenotype, our results are consistent with the hypothesis that Treg cells maintain autoreactive T cells in the anergic state, but these can be released from anergy by products of the innate immune system (e.g., CpG) which override regulatory mechanisms that maintain immune homeostasis.